What are the other Names for this Condition? (Also known as/Synonyms)

• HISN (Heparin-Induced Skin Necrosis)

What is Heparin-Induced Skin Necrosis? (Definition/Background Information)

• Heparin is a blood-thinner (anticoagulant) medication that is administered in the treatment of thromboembolic disorders (clotting disorders such as deep vein thrombosis). Heparin is also prescribed as an effective prophylaxis towards preventing several other medical conditions
• Heparin-Induced Skin Necrosis (HISN) is a rare adverse reaction of the body to heparin injections, administered intravenously or subcutaneously, resulting in severe skin signs and symptoms. The skin turns red at the injection site with the formation of inflammatory blisters that later necrotize (leading to cell death)
• Discontinuation of heparin immediately on recognizing/diagnosing condition can help in a complete resolution. In such cases, the prognosis of Heparin-Induced Skin Necrosis is generally excellent. Nevertheless, individuals may need to be prescribed an alternative anticoagulant medication to prevent blood clots from forming

Who gets Heparin-Induced Skin Necrosis? (Age and Sex Distribution)

• Individuals of all ages may be affected, although most cases of Heparin-Induced Skin Necrosis are noted in adults
• Both males and females may be affected; for some reason, the condition is mostly noted in middle-aged women
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Heparin-Induced Skin Necrosis? (Predisposing Factors)

• The key risk factor for Heparin-Induced Skin Necrosis is the use of heparin (to treat certain health issues) that results in the skin condition as a side effect

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Heparin-Induced Skin Necrosis? (Etiology)

Heparin-Induced Skin Necrosis (HISN) develops from heparin injections administered for various clotting disorders or prophylactically (as a preventive measure). It is important to note that a vast majority of individuals administered heparin are not affected by the drug.

The proposed mechanisms to explain HISN include:

• Immune-mediated response of the body
• Formation of antigen-antibody complexes
• Incorrect procedure of injecting heparin
• Fat tissue at injection site causing persistence of heparin at the site due to poor (local) blood circulation

Generally, HISN develops 5-11 days (average 7 days) after the subcutaneous or intravenous injection of heparin. In cases where the individual is already sensitized to heparin, the skin signs and symptoms may develop almost immediately (within a few hours). In rare cases, a delayed onset of the condition (after several months) is seen.

What are the Signs and Symptoms of Heparin-Induced Skin Necrosis?

The signs and symptoms of Heparin-Induced Skin Necrosis may vary from one individual to another. It may be mild or severe and related to the usage (dose) of the drug. The condition is known to get better after stoppage of the offending medication.

The signs and symptoms may include:

• Pain, redness, and swelling at the site of heparin injection, after about a week or so
• The skin appears like it is bruised; the site of injection may be the arm, thigh, or abdomen
• Rarely, skin sites at other body locations (away from the injection site) may be involved
• Blister formation is noted in 24-48 hours or less
• Following this, the skin cells die (skin necrosis occurs) and a dark/black center is observed

The size of necrotic involvement may vary but are usually a few centimeters across (average 3 cm). In some cases, an extensive involvement of the skin is noted.

How is Heparin-Induced Skin Necrosis Diagnosed?

It is generally difficult and may be challenging to diagnose Heparin-Induced Skin Necrosis (HISN), especially if other medications are being taken by the individual and if the skin lesions site is away from the heparin administration site.

HISN is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation (including evaluating for heparin administration, current medications in use, etc.)
• Assessment of the presenting signs and symptoms
• Imaging studies, if necessary
• Laboratory blood tests such as protein C and protein S
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Skin biopsy: A skin tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Heparin-Induced Skin Necrosis?

The complications of Heparin-Induced Skin Necrosis (HISN) may include:

• Anaphylactoid reactions causing fever, low blood pressure, chest pain, and labored breathing
• Severe HISN due to extensive involvement of the skin
• Delayed recognition of HISN resulting in a more severe condition
• Development of other conditions due to heparin exposure such as heparin-induced thrombocytopenia and acute urticaria

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Heparin-Induced Skin Necrosis Treated?

The treatment for Heparin-Induced Skin Necrosis may include one or more of the following measures, depending on the severity of signs and symptoms:

• Discontinuation of heparin
• If an anticoagulant medication is deemed necessary; then, the use of alternate medications such as warfarin or lepirudin
• Wound care, which includes cleaning and dressing the skin lesion sites
• Surgical debridement of necrotic tissue, if necessary
• Skin grafting if a large skin area was involved

How can Heparin-Induced Skin Necrosis be Prevented?

Heparin-Induced Skin Necrosis may be preventable, by avoiding anticoagulation medication containing heparin in some individuals.

What is the Prognosis of Heparin-Induced Skin Necrosis? (Outcomes/Resolutions)

The prognosis of Heparin-Induced Skin Necrosis is dependent upon the severity of the signs and symptoms and associated complications.

• However, in most cases, following stoppage of the offending medication, the condition tends to resolve completely
• Rarely, due to extensive involvement of the skin and a delayed diagnosis/treatment of heparin, the outcomes may be fatal

Additional and Relevant Useful Information for Heparin-Induced Skin Necrosis:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/healthy-living/skin-disorders/